Medical News Stories
Dexmedtomidine vs Midazolam or Propofol for Sedation During Prolonged Mechanical Ventilation
Study Questions: Does dexmedetomidine (DEX) maintain target sedation as well as midazolam (MID) and propofol (PRO)? Is DEX associated with decreased duration of mechanical ventilation?
Study Description: Two parallel, randomized, double-blind multicenter trials were conducted in ICU patients requiring mechanical ventilation and continuous sedation. Exclusion criteria included severe neurological disorder or hemodynamic instability. Patients were randomized to receive DEX 0.2-1.4 mcg/kg/hr or a comparator, MID 0.03-0.2 mg/kg/hr (MIDEX trial) or PRO 5-67 mcg/kg/min (PRODEX trial). Time within the target Richmond Agitation Sedation Scale (RASS) score range of 0 to -3 without rescue medication and duration of mechanical ventilation were the primary outcome parameters.
Results: DEX was noninferior to MID and PRO for time within target RASS range. The median duration of mechanical ventilation was significantly less in the MIDEX trial (DEX: 123 h, MID: 164 h; p = 0.03) but not in the PRODEX trial (DEX: 97 h, PRO: 118 h; p = 0.24). The median time to extubation was reduced with DEX in both MIDEX (DEX: 101 h, MID: 147 h; p = 0.01) and PRODEX (DEX: 69 h, PRO: 93 h; p = 0.04) trials. Hypotension (DEX: 20.6%, MID: 11.6%; p = 0.007) and bradycardia (DEX: 14.2%, MID: 5.2%; p < 0.001) occurred more frequently in the DEX group in the MIDEX trial. First-degree heart block (DEX: 3.7%, PRO: 0.8%; p = 0.04), critical illness polyneuropathy (DEX: 0.8%, PRO: 4%; p = 0.02) and neurocognitive adverse effects (DEX: 18%, PRO: 29%; p = 0.008) including delirium were significantly different in the PRODEX trial.
Conclusion(s): DEX maintained target sedation as well as MID and PRO. DEX was associated with a reduced duration of mechanical ventilation when compared with MID but not PRO.
Perspective: While the authors’ conclude that DEX is feasible for long-term sedation, the median DEX exposure in both trials was only 42 h. Sedation interruption was used in approximately 90% of patients in each cohort, while spontaneous breathing trials only occurred in about 50% of cases. The cardiac adverse event profile of DEX was similar to previous studies. Interestingly, DEX and MID had similar rates of delirium while PRO had higher rates of delirium when compared to DEX, although Confusion Assessment Method for the ICU (CAM-ICU) was assessed only once – 48 h after study drug discontinuation – raising questions about the ability to extrapolate to the incidence of delirium overall during patients’ stays in the ICU (were CAM-ICU values comparable or different between groups at times other than the 48-h mark?).